Research Projects

How does the TDP-43 protein go wrong in frontotemporal dementia?

Francesco Aprile

Awarded to:
Dr Francesco Aprile

Current award:

Imperial College London

1 March 2020 - 29 February 2024

Full project name:

Understanding the role of pathological cleavage in TDP-43 phase-separation






Frontotemporal dementia (FTD) is a relatively rare form of dementia and is thought to account for fewer than one in 20 of all dementia cases.

One of the key hallmarks of FTD is the build-up of toxic protein clumps in the brain.

Scientists don’t yet fully understand how and why these protein clumps form, and this gap in our knowledge makes it challenging for researchers to design potential drugs to prevent this protein build up.

The proteins that cause nerve cell damage are not the same for all people with FTD, but one of the key proteins that can form clumps is TDP-43.

Our cells can cut TDP-43 protein into different sized pieces, and TDP-43 protein fragments have been found in clumps from people with FTD alongside the full-size protein.

Scientists think that these small fragments of TDP-43 can trigger the creation of toxic protein clumps that damage and destroy brain cells, but it is unclear how. Dr Francesco Aprile and his team aim to answer this question.

This improved understanding will put scientists in a much better place to design drugs to help protect the brain.

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